1. Field of the Invention
The present invention generally relates to the treatment of movement disorders in a patient suffering or susceptible to same, by administration to a patient of an effective amount of a neurotransmission modulating composition. More specifically, the invention relates to such treatment using a neurotransmission modulating composition comprising a 5HT- and/or .alpha..sub.2 antagonist.
2. Description of the Related Art
Movement disorders include a wide variety of disease states and physiological conditions. Examples include various dyskinesias involving excessive or otherwise abnormal involuntary movement, which may vary significantly in rate, frequency, periodicity and progressionary character, and which may encompass disorders such as tremors, akathisias, asterixis, athetosis, choreaathetosis, tics, chorea/choreaform movements, dystonias, spasticity, restless legs syndrome, hyperkinetic movement disorders, hemiballismus, myoclonus, tardive dyskinesia and other types of dyskinesias.
Tremors types are particularly varied, and include for example Parkinsonian tremors, rubral tremors, post-traumatic tremors, drug-induced tremors (e.g. induced by lithium or other drug agents), cerebellar tremors associated with lesions of the cerebellum or cerebellar outflow pathway, Tourette syndroinal tremors and other peripheral neuropathy-associated tremors.
These disorders, particularly dyskinetic conditions associated with neurological impairment of the basal ganglia, are far from uncommon in the general population. Approximately 1.5 million people are estimated to suffer from Parkinsonian tremor or essential tremor in the United States alone. The etiology of such physiologic states is poorly understood, involving striata comprising dopaminergic pathways whose transductional characteristics, neurotransmitter components and receptor mechanisms are ill-defined but constitute the focus of intensive research efforts directed to their elucidation.
Parkinson's tremor is a dyskinetic condition typically presenting as a resting tremor that is less pronounced, for example, when a person lifts his/her hand. Parkinson's tremor sometimes responds to L-DOPA, the classical treatment for the other symptoms of Parkinson's Disease (PD), but the tremor component is the most difficult symptom of the disease to treat effectively.
Levodopa-induced dyskinesias occur later in Parkinson's Disease and are extremely handicapping. Such dyskinesias range from subtle undulating movements of the body to wild uncontrollable swinging movements of the limbs that can literally knock a seated patient out of his or her chair and often makes it impossible for patients to feed themselves or perform other basic tasks requiring rudimentary manual dexterity and motor coordination.
Essential tremor and familial tremor are the same disease state in physiological manifestation, with familial tremor referring to the genetically-based incidence of such disease state. Essential tremor is the most common type of tremor; it can co-exist with PD tremor but is a categorically separate disease state.
Tremor is a pervasive movement disorder, for which few efficacious therapeutic agents presently exist, and there are iany di fferent types of this dyskinetic condition.
A concise overview of tremor varieties is located at the World Wide Web site http://www.geocities.com/.about.shaky-mtl/Newpage95.htm. Epidemiology charts for incidence of tremor are presented at the World Wide Web site http://www.geocities.com/.about.shaky-mtl/Newpage118.htm.
In the area of therapeutic compositions for treatment of movement disorders, there are few agents with demonstrated utility, and many of such agents have unacceptable side effect profiles.
Considering the therapeutic agents that have been used or proposed for treatment, beta-blockers such as Inderal have been used for essential tremor. Some secondary drugs are available, but they have generally poor efficacy. The mechanism of essential tremor is unknown and is probably not related to dopamine, since essential tremor does not respond to therapeutic agents that are generally used for treatment of Parkinson's Disease.
Recently, implantable electrodes in the brain have been used as a therapeutic intervention for Parkinson's tremor. This approach, however, is expensive and requires invasive techniques for placement in the basal ganglia and thalamus.
There is thus a compelling need in the art for efficacious therapeutic agents to treat movement disorders in all their variant forms.